Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Fructosediphosphates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,441 records · Page 80Linked to original sources
PubMed1981

Fructose 2,6-bisphosphate. A new activator of phosphofructokinase.

A new activator of rat liver phosphofructokinase was partially purified from rat hepatocyte extracts by DEAE-Sephadex chromatography. The activator, which eluted in the sugar diphosphate region, was sensitive to acid treatment but resistant to heating in alkali. Mild acid hydrolysis resulted in the appearance of a sugar monophosphate which was identified as fructose 6-phosphate by gas chromatography/mass spectroscopy. These observations suggest that the activator is fructose 2,6-bisphosphate. This compound was synthesized by first reacting fructose 1,6-bisphosphate with dicyclohexylcarbodiimide and then treating the cyclic intermediate with alkali. The structure of the synthetic compound was definitively identified as fructose 2,6-bisphosphate by 13C NMR spectroscopy. Fructose 2,6-bisphosphate had properties identical with those of the activator purified from hepatocyte extracts. It activated both the rat liver and rabbit skeletal muscle enzyme in the 0.1 microM range and was several orders of magnitude more effective than fructose 1,6-bisphosphate. Fructose 2,6-bisphosphate was not a substrate for aldolase or fructose 1,6-bisphosphatase. It is likely that this new activator is an important physiologic factor of phosphofructokinase in vivo.

Animals↗
PubMed1981

Age and the control of glycolysis in the rat lens.

Previous studies with lens dispersions indicated that the rate-limiting step in glycolysis shifts from hexokinase (HK) in the young lens to phosphofructokinase (PFK) in older lenses. Because the concentrations of the complex controlling factor for these enzymes could not be reproduced reliably in homogenates, the question of age-related control of glycolysis was re-examined in intact lenses. Toward this end, the levels of several metabolites of glucose were measured in fresh and incubated clear lenses. Of the substrates measured per fresh lens, only one changed significantly with age; fructose diphosphate was increased. When lenses were incubated in 2 to 12 mM glucose, the lactate production per lens was not significantly different with age. Together these results suggested that the glycolytic mass of the lens was constant with age. In both young and older lenses, increases in glucose in the medium led to increases in both glucose and glucose-6-phosphate in the lens. The lack of corresponding increase in lactate production suggested that the regulatory step lay downstream from HK, probably at PFK. This finding was corroborated by evidence that the initial acceleration of lactate production by the addition of cyanide (the Pasteur effect) was accompanied by decreases in the substrates of PFK, glucose-6-phosphate and fructose-6-phosphate. A secondary disinhibition of HK, as indicated by decreased lens glucose, became apparent after longer incubation with cyanide. This suggested that after disinhibition of PFK, HK became rate-limiting until the level of glucose-6-phosphate fell enough to allow the disinhibition of the latter enzyme as well. Thus PFK seemed to be the primary regulatory step in aerobic glycolysis in lenses of rats from 1 to 12 months of age.

Aging↗
PubMed1981

A novel enzyme catalyzes the synthesis of activation factor from ATP and D-fructose-6-P.

We have recently discovered an activator for phosphofructokinase termed "activation factor" (Furuya, E., and Uyeda, K. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 5861-5864). In this paper, we investigated the enzyme responsible for its synthesis. We have found an enzyme from rat liver which catalyzes the formation of activation factor from fructose-6-P and ATP-Mg and it has been identified as fructose-2,6-P2. Fructose-1,6-P2, fructose-1-P, or fructose does not serve as a substrate. This enzyme has been partially purified and shown to be different from phosphofructokinase. Several lines of evidence indicate that the in vitro synthetic product is identical with chemically synthesized fructose-2,6-P2: (a) it is active in our assay for activation factor which is based on counteraction of ATP inhibition of phosphofructokinase; (b) it is acid labile as is fructose-2,6-P2; and (c) it shows the same mobility as synthetic fructose-2,6-P2 upon paper chromatography and the acid hydrolysis product has been identified as fructose-6-P. Thus, this new enzyme catalyzes the synthesis of the activation factor from fructose-6-P and ATP-Mg.

Adenosine Triphosphate↗
PubMed1981

The effect of natural and synthetic D-fructose 2,6-bisphosphate on the regulatory kinetic properties of liver and muscle phosphofructokinases.

The effect of natural "activation factor" and synthetic fructose-2,6-P2 on the allosteric kinetic properties of liver and muscle phosphofructokinases was investigated. Both synthetic and natural fructose-2,6-P2 show identical effects on the allosteric kinetic properties of both enzymes. Fructose-2,6-P2 counteracts inhibition by ATP and citrate and decreases the Km for fructose-6-P. This fructose ester also acts synergistically with AMP in releasing ATP inhibition. The Km values of liver and muscle phosphofructokinase for fructose-2,6-P2 in the presence of 1.25 mM ATP are 12 milliunits/ml (or 24 nM) and 5 milliunits/ml (or 10 nM), respectively. At near physiological concentrations of ATP (3 mM) and fructose-6-P (0.2 mM), however, the Km values for fructose-2,6-P2 are increased to 12 microM and 0.8 microM for liver and muscle enzymes, respectively. Thus, fructose-2,6-P2 is the most potent activator of the enzyme compared to other known activators such as fructose-1,6-P2. The rates of the reaction catalyzed by the enzymes under the above conditions are nonlinear: the rates decelerate in the absence or in the presence of lower concentrations of fructose-2,6-P2, but the rates become linear in the presence of higher concentrations of fructose-2,6-P2. Fructose-2,6-P2 also protects phosphofructokinase against inactivation by heat. Fructose-2,6-P2, therefore, may be the most important allosteric effector in regulation of phosphofructokinase in liver as well as in other tissues.

Adenosine Monophosphate↗
PubMed1981

The structure of "activation factor" for phosphofructokinase.

The "activation factor" for phosphofructokinase was shown by chemical analysis, by synthesis, and by 13C NMR spectroscopy to be beta-D-fructose-2,6-P2. This compound was prepared from D-fructose-1,2-cyclic 6-P2 by alkaline hydrolysis. D-Fructose-1,2-cyclic 6-P2 is ineffective in activating phosphofructokinase while synthetic D-fructose-2,6-P2 has the same specific activity toward phosphofructokinase as the "activation factor" isolated from rat liver, and it exhibits the same characteristics on paper and ion exchange chromatography. Acid treatment of both the synthetic and the natural product destroys the biological activity and yields 1 mol each of fructose-6-P and Pi; alkaline phosphatase treatment of the compound followed with acid hydrolysis yields fructose. The natural abundance 13C NMR spectra of the synthetically prepared and purified D-fructose-1,2-cyclic 6-P2 and D-fructose-2,6-P2 have been obtained and all resonances have been assigned. The spectra also show that both samples contain predominantly one anomer and the 13C chemical shifts and 31P-13C coupling constants are consistent only with the beta-anomer.

Animals↗
PubMedDate not supplied

Restoration of blood 2,3-diphosphoglycerate levels in multi-transfused patients: effect of organic and inorganic phosphate.

Blood stored in acid-citrate-dextrose (ACD) shows a progressive decrease in 2,3-diphosphoglycerate (DPG) content. Since the decrease in DPG increases hemoglobin oxygen affinity, which in turn may reduce tissue and venous PO2 and peripheral oxygen delivery, many efforts have been made to preserve or restore DPG levels in stored blood. An in vivo rejuvenating technique, employing fructose-1,6-diphosphate (FDP) at a mean dosage of 1 mmol kg-1 day-1 of phosphate, to increase the DPG circulating level in multi-transfused patients is proposed. Eighteen patients, who received at least one-third of their estimated blood volume (3990 +/- 480 (SEM) ml of ACD stored blood) in blood transfusion, were treated: nine with inorganic phosphate, and nine with FDP. Basal DPG was very low in both groups: 12.61 +/- 1.34 (SEM) and 10.42 +/- 0.98 (SEM) mumol g-1, respectively (normal value is 14.5 mumol g-1, at pH 7.40). However, DPG values increased significantly and promptly in patients receiving FDP, whereas in cases of inorganic phosphate administration, it was not significantly raised over the basal value until the third day. Phosphatemia remained normal and constant with FDP, but it rose significantly on the third day of treatment with inorganic phosphate. FDP appears to consistently and rapidly increase DPG levels after transfusion with blood stored in ACD, and to be particularly safe.

2,3-Diphosphoglycerate↗
PubMed1983

Pyruvate kinase isozyme (PK-Greenville) with defective allosteric activation by fructose-1,6-diphosphate: the role of F-1,6-P modulation in normal erythrocyte metabolism.

A child with chronic hemolytic anemia since birth was found to have erythrocyte pyruvate kinase (PK) in a highly unusual form relative to other mutant isozymes when characterized by International Committee for Standardization in Hematology criteria. Most properties of the partially purified isozyme (designated PK-Greenville) were altered minimally, if at all, except for nearly total insensitivity to allosteric activation by fructose-1,6-diphosphate (F-1,6-P). One parent appeared to be heterozygous for a null gene and the other for an allele governing production of the mutant isozyme. Apparent restriction of the molecular defect to ineffective activation kinetics suggests that the F-1,6-P binding site on erythrocyte PK is functionally as well as physically allosteric. The magnitude of the metabolic block at the PK step and the clinical severity indicate that allosteric modulation by F-1,6-P is a crucial property of PK in normal erythrocyte metabolism.

Adenosine Diphosphate↗
PubMed1983

The effects of fructose-1,6-diphosphate on the isolated rabbit heart.

The effects of 0.1-100 mgm of fructose-1,6-diphosphate (FDP) were observed on the inotropic and chronotropic activity of the isolated, perfused rabbit heart, using a modified Langendorff technique. The preparations were treated with bolus injections of 0.1-100 mgm of FDP in gradually increasing concentrations following their recovery from previous injections. FDP produced a biphasic inotropic response with an initial decrease in contractility followed by an increase. The largest increases in contractility were observed at concentrations below 25 mgm while the greatest decreases occurred at the higher doses. The average maximal increase in contractility was 136.5 +/- 24% at an average dose of 1.53 +/- 0.6 mgm FDP. The average maximal decrease in the inotropic activity was 69 +/- 3% which was observed at an average dose of 92 +/- 8 mgm FDP. Recovery of the contractile activity following the observed effects of FDP was greater than or equal to pretreatment levels at all concentrations except 0.5 and 100 mgm FDP. The basal tone or tension of some hearts, especially after high doses of FDP, increased with some of these preparations contracting into a hard, putty-colored knot. FDP was also observed to exert an anti-arrhythmic effect on arrhythmic hearts. A negative chronotropic response was noted at all concentrations of FDP while a positive chronotropic response was observed only at the 0.1 mgm dose of FDP. The average increases and decreases in heart rate were 65 +/- 18 and 37 +/- 7%, respectively, at average respective doses of 9 +/- 6 and 40 +/- 15 mgm FDP. These data indicate that FDP exerts biphasic inotropic and chronotropic effects as well as an anti-arrhythmic effect on the isolated myocardium. They also indicate that FDP is toxic at higher cumulative doses.

Animals↗
PubMed1983

In vitro effects of fructose-1,6-diphosphate on oxygen affinity and electrolyte equilibrium in human blood.

The in vitro effects of a solution of fructose-1,6-diphosphate on hemoglobin-oxygen affinity and electrolyte distribution between plasma and red cells were evaluated. Fructose-1,6-diphosphate increased intracellular pH and decreased extracellular pH. There were no shifts in Na+, K+, Ca++ and Cl- between plasma and red cells. Red cell content of 2,3-diphosphoglycerate remained unchanged, while P50 was reduced (as a consequence of the intracellular alkalosis). The therapeutical implications of these results are discussed.

2,3-Diphosphoglycerate↗
PubMedDate not supplied

[Influence of several metabolites on A4 and B4-isoenzymes of loach lactate dehydrogenase activity depending on the direction of the isoenzyme-catalyzed reaction].

Various concentration of fructose-1.6-diphosphate, malate, oxaloacetate, creatine phosphate, ATP, ADP and AMP were studied for their effect on the activity of A4-and B4-isoenzymes of lactate dehydrogenase (LDH, EC 1, 1. 1. 27) produced from skeletal muscles and unfertilized egg cells of Misgurnus fossilis in the reactions of lactate oxidation and pyruvate reduction. It was found that oxaloacetate, creatine phosphate, ADP and AMP decreased the activity of A- and B-type isoenzymes to a different extent. The value of the inhibitory action depended not only on the concentration of the substances and subunit composition of the isoenzymes but also depended on the direction of the reaction they catalyse. Malate and fructose-1.6-diphosphate did not inhibit the activity of A4 isoenzyme in the lactate oxidation and malate and ATP did not influence the activity of the former and of B4-isoenzymes in this reaction. At the same time malate, fructose-1.6-diphosphate and ATP decreased the activity of the investigated isoenzymes in the pyruvate reduction reactions.

Adenine Nucleotides↗
PubMed1983

The influence of glucocorticoids on hepatic glycolytic intermediates in fed peritonitis rats.

Earlier work on fasted endotoxemic and septic rats suggested that glucocorticoid pretreatment improved survival by promoting gluconeogenesis. The possible mechanism of this therapeutic effect was investigated in fed peritonitis septic rats, which are in a predominantly glycolytic mode of metabolism. Fed adult male rats (185-255 g) received cecal incisions or sham operations under ether with or without simultaneous IV injection of dexamethasone (DMS) (1.0 mg/100 g rat). Liver was sampled by freeze-clamping at 5 h, and glycolytic intermediates were determined by UV spectrophotometry. The high-energy intermediate, phosphoenol-pyruvate (PEP), fell 57% to 76 +/- 83 nmole/g wet liver (+/- 1 SD) in the fed peritonitis group; nine of 13 rats had PEP values at least 50% below mean control concentrations. Fasted septic rats (N = 26) do not have decreased PEP levels. Glucocorticoids were protective in the fed septic rats; only five of 17 DMS-pretreated rats had PEP fall below 50% of the fed normals. A significant finding was the decline in fructose diphosphate (FDP) from 32 +/- 9 nmole in fed shams (N = 12) to 21 +/- 11 nmole/g wet liver with DMS-pretreated fed shams (N = 15). This suggests that DMS may be inhibiting the glycolytic enzyme, phosphofructokinase, and thereby enhancing gluconeogenesis by sparing hexose monophosphates. Lactate in fed sham liver was 1,869 +/- 336 nmole/g, a concentration twofold greater than in fasted liver. This difference may contribute to the increased vulnerability of fed rats to septic shock. It is concluded that glucocorticoids tend to normalize Embden-Meyerhof pathway intermediates in both fed and fasted rat livers.

Animals↗